Abstract

Background Crizotinib, a dual anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitor,
is currently being evaluated for the treatment of neuroblastoma. Its effects are thought to be mediated mainly via its activity
against ALK. Although MET genomic/protein expression status might conceivably affect crizotinib efficacy, this issue has hitherto
not received attention in neuroblastomas.

Aims/Methods MET genomic and protein expression status was characterised by silver in situ hybridisation and immunohistochemistry (IHC)
respectively, in a cohort of 54 neuroblastoma samples. MET splice isoforms were characterised in 15 of these samples by quantitative
PCR.

Conclusions MET amplification and protein expression, although low in prevalence, are present in neuroblastomas. This has implications
when crizotinib is employed as a therapeutic agent in neuroblastomas. Additionally, the existence of alternatively spliced
MET isoforms may have clinical and biological implications in neuroblastomas.